The major neuropsychiatric complication in HIV-disease is cognitive-motor impairment, with HIV-1 seropositive drug users reported to be at higher risk for the development of HIV-associated dementia and more rapid progression in neurologic disability. Oxidative stress, which can lead to neuronal degeneration, is increased in HIV-1 disease and appears to be potentiated by drugs of abuse. The primary objective of this ancillary study is to determine whether supplementation with selenium, a biologic antioxidant that is required for protecting cells from oxidative damage, can provide neuroprotection and help maintain cognitive function in HIV-l seropositive chronic drug users. Supplementation with selenium has been shown to improve oxidative defense systems in HIV/AIDS patients, and inhibit mental deterioration in neurologic patients. Our preliminary investigations in HIV- l infected drug users indicate that low levels of selenium are associated with decreased mental performance, and that short-term selenium supplementation results in a strong potential for improvement in mental function and mood state. These data suggest that administration of selenium may be an effective strategy to prevent loss of cognitive ability. We propose to extend our currently NIDA-funded, clinical trial, "Selenium Therapy to Slow Disease Progression in HIV+ IDUs", to compare the effects of selenium or placebo on neuropsychological function. Consented HIV-l infected drug users (n=120) will be enrolled at the baseline visit of the parent study, prior to supplementation, and administered a psychosocial and cognitive battery every 6 months for 30 months. Drug use, nutritional, immunologic, oxidative stress, and health status data will be collected by the parent study at the same visit as the cognitive and psychosocial battery, and made available for the proposed project. There is no direct scientific overlap between the two studies. The proposed collaborative and cost-effective research provides a unique opportunity to further our understanding of neuropsychological function in HIV-l seropositive men and women who abuse drugs, as well as provide important information necessary for the management of cognitive impairment in HIV-1 disease.